scholarly journals Blood metabolome signature predicts gut microbiome α-diversity in health and disease

2019 ◽  
Author(s):  
Tomasz Wilmanski ◽  
Noa Rappaport ◽  
John C. Earls ◽  
Andrew T. Magis ◽  
Ohad Manor ◽  
...  
Keyword(s):  
Microbial Diversity ◽  
Gut Microbiome ◽  
Laboratory Tests ◽  
Clinical Laboratory ◽  
The Body ◽  
Community Diversity ◽  
Blood Metabolites ◽  
Α Diversity ◽  
Host Health ◽  
Host Physiology

AbstractDefining a ‘healthy’ gut microbiome has been a challenge in the absence of detailed information on both host health and microbiome composition. Here, we analyzed a multi-omics dataset from hundreds of individuals (discovery n=399, validation n=540) enrolled in a consumer scientific wellness program to identify robust associations between host physiology and gut microbiome structure. We attempted to predict gut microbiome α-diversity from nearly 1000 analytes measured from blood, including clinical laboratory tests, proteomics and metabolomics. While a broad panel of 77 standard clinical laboratory tests and a set of 263 proteins from blood could not accurately predict gut microbial α-diversity, we found that 45% of the variance in microbial community diversity was explained by a subset of 40 blood metabolites, many of microbial origin. This relationship between the host metabolome and gut microbiome α-diversity was very robust, persisting across disease conditions and antibiotics use. Several of these novel metabolic biomarkers of gut microbial diversity were previously associated with host health (e.g. cardiovascular disease risk, diabetes, and kidney function). A subset of 11 metabolites classified participants with potentially problematic low α-diversity (ROC AUC=0.88, Precision-Recall AUC=0.76). Relationships between host metabolites and α-diversity remained consistent across most of the Body Mass Index (BMI) spectrum, but were modified in extreme obesity (class II/III, but not class I), suggesting a significant metabolic shift. Out-of-sample prediction accuracy of α-diversity from the 40 identified blood metabolites in a validation cohort, whose microbiome samples were analyzed by a different vendor, confirmed the robust correspondence between gut microbiome structure and host physiology. Collectively, our results reveal a strong coupling between the human blood metabolome and gut microbial diversity, with implications for human health.

scholarly journals Mass Azithromycin Distribution and Community Microbiome: A Cluster-Randomized Trial

2018 ◽  
Vol 5 (8) ◽  
Author(s):  
Thuy Doan ◽  
Armin Hinterwirth ◽  
Ahmed M Arzika ◽  
Sun Y Cotter ◽  
Kathryn J Ray ◽  
...  
Keyword(s):  
Preschool Children ◽  
Gut Microbiome ◽  
Controlled Trial ◽  
Community Level ◽  
Childhood Mortality ◽  
Community Diversity ◽  
Secondary Outcome ◽  
Α Diversity ◽  
Cluster Randomized

Abstract Background Mass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community’s gut microbiome at 6 months after the last distribution. Methods In this cluster-randomized controlled trial, children aged 1–60 months in the Dossa region of Niger were randomized at the village level to receive a single dose of azithromycin or placebo every 6 months. Fecal samples were collected 6 months after the second treatment for metagenomic deep sequencing. The prespecified primary outcome was the Euclidean PERMANOVA of the gut microbiome, or effectively the distance between the genus-level centroid at the community level, with the secondary outcome being the Simpson’s α diversity. Results In the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, P < .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson’s index, P = .005). Conclusions Two mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality. Clinical Trials Registration NCT02048007.

scholarly journals Gut microbiome features associated withClostridium difficilecolonization in puppies

2019 ◽  
Author(s):  
Alexander S. Berry ◽  
Denise Barnhart ◽  
Brendan J. Kelly ◽  
Donna J. Kelly ◽  
Daniel P. Beiting ◽  
...  
Keyword(s):  
Bacterial Community ◽  
Microbial Diversity ◽  
Gut Microbiome ◽  
Statistical Significance ◽  
Random Effect ◽  
Mixed Effects ◽  
Community Diversity ◽  
Bacterial Community Diversity ◽  
Gut Microbial Community ◽  
Colonization Status

AbstractIn people, colonization withClostridium difficile, the leading cause of antibiotic-associated diarrhea, has been shown to be associated with distinct gut microbial features, including reduced bacterial community diversity and depletion of key taxa. In dogs, the gut microbiome features that defineC. difficilecolonization are less well understood. We sought to define the gut microbiome features associated withC. difficilecolonization in puppies, a population where the prevalence ofC. difficilehas been shown to be elevated, and to define the effect of puppy age and litter upon these features andC. difficilerisk. We collected fecal samples from weaned (n=27) and unweaned (n=74) puppies from 13 litters and analyzed the effects of colonization status, age and litter on microbial diversity using linear mixed effects models.Colonization withC. difficilewas significantly associated with younger age, and colonized puppies had significantly decreased bacterial community diversity and differentially abundant taxa compared to non-colonized puppies, even when adjusting for age.C. difficilecolonization remained associated with decreased bacterial community diversity, but the association did not reach statistical significance in a mixed effects model incorporating litter as a random effect.Even though litter explained a greater proportion (67%) of the variability in microbial diversity than colonization status, we nevertheless observed heterogeneity in gut microbial community diversity and colonization status within more than half of the litters, suggesting that the gut microbiome contributes to colonization resistance againstC. difficile. The colonization of puppies withC. difficilehas important implications for the potential zoonotic transfer of this organism to people. The identified associations point to mechanisms by whichC. difficilecolonization may be reduced.

scholarly journals Desulfovibrio is not always associated with adverse health effects in the Guangdong Gut Microbiome Project

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12033
Author(s):  
Yi-ran Chen ◽  
Qin-long Jing ◽  
Fang-lan Chen ◽  
Huimin Zheng ◽  
Li-dan Chen ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
Large Scale ◽  
Community Diversity ◽  
Human Populations ◽  
Human Intestine ◽  
Adverse Health Effects ◽  
Waist Size ◽  
Host Health ◽  
The Relationship

Desulfovibrio (DSV) is frequently found in the human intestine but limited knowledge is available regarding the relationship between DSV and host health. In this study, we analyzed large-scale cohort data from the Guangdong Gut Microbiome Project to study the ecology of DSV and the associations of DSV and host health parameters. Phylogenetic analysis showed that Desulfovibrio piger might be the most common and abundant DSV species in the GGMP. Predominant sub-OTUs of DSV were positively associated with bacterial community diversity. The relative abundance of DSV was positively correlated with beneficial genera, including Oscillospira, Coprococcus,Ruminococcus,Akkermansia, Roseburia,Faecalibacterium, andBacteroides, and was negatively associated with harmful genera, such as Clostridium,Escherichia,Klebsiella, and Ralstonia. Moreover, the relative abundance of DSV was negatively correlated with body mass index, waist size, triglyceride levels, and uric acid levels. This suggests that DSV is associated with healthy hosts in some human populations.

scholarly journals Bridging Rare and Abundant Bacteria with Ecosystem Multifunctionality in Salinized Agricultural Soils: from Community Diversity to Environmental Adaptation

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Wenjie Wan ◽  
Song Liu ◽  
Xiang Li ◽  
Yonghui Xing ◽  
Wenli Chen ◽  
...  
Keyword(s):  
Bacterial Community ◽  
Variable Selection ◽  
Microbial Diversity ◽  
Community Assembly ◽  
Agricultural Soils ◽  
Environmental Adaptation ◽  
Community Diversity ◽  
Soil Restoration ◽  
Α Diversity ◽  
Ecosystem Multifunctionality

ABSTRACT Bacterial diversity and ecosystem multifunctionality (EMF) vary along environmental gradients. However, little is known about interconnections between EMF and taxonomic and phylogenetic diversities of rare and abundant bacteria. Using MiSeq sequencing and multiple statistical analyses, we evaluated the maintenance of taxonomic and phylogenetic diversities of rare and abundant bacteria and their contributions to EMF in salinized agricultural soils (0.09 to 19.91 dS/m). Rare bacteria exhibited closer phylogenetic clustering and broader environmental breadths than abundant ones, while abundant bacteria showed higher functional redundancies and stronger phylogenetic signals of ecological preferences than rare ones. Variable selection (86.7%) dominated rare bacterial community assembly, and dispersal limitation (54.7%) and variable selection (24.5%) determined abundant bacterial community assembly. Salinity played a decisive role in mediating the balance between stochastic and deterministic processes and showed significant effects on functions and diversities of both rare and abundant bacteria. Rare bacterial taxonomic α-diversity and abundant bacterial phylogenetic α-diversity contributed significantly to EMF, while abundant bacterial taxonomic α-diversity and rare bacterial phylogenetic α-diversity did not. Additionally, abundant rather than rare bacterial community function had a significant effect on soil EMF. These findings extend our knowledge of environmental adaptation of rare and abundant bacteria and highlight different contributions of taxonomic and phylogenetic α-diversities of rare and abundant bacteria to soil EMF. IMPORTANCE Soil salinization is a worldwide environmental problem and threatens plant productivity and microbial diversity. Understanding the generation and maintenance of microbial diversity is essential to estimate soil tillage potential via investigating ecosystem multifunctionality. Our sequence-based data showed differences in environmental adaptations of rare and abundant bacteria at taxonomic and phylogenetic levels, which led to different contributions of taxonomic and phylogenetic α-diversities of rare and abundant bacteria to soil EMF. Studying the diversity of rare and abundant bacteria and their contributions to EMF in salinized soils is critical for guiding soil restoration.

scholarly journals Controlled Complexity: Optimized Systems to Study the Role of the Gut Microbiome in Host Physiology

2021 ◽  
Vol 12 ◽  
Author(s):  
Robert W. P. Glowacki ◽  
Morgan J. Engelhart ◽  
Philip P. Ahern
Keyword(s):  
Gut Microbiome ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Human Microbiome ◽  
Model Systems ◽  
Wild Mice ◽  
Host Health ◽  
Host Physiology ◽  
The Impact

The profound impact of the gut microbiome on host health has led to a revolution in biomedical research, motivating researchers from disparate fields to define the specific molecular mechanisms that mediate host-beneficial effects. The advent of genomic technologies allied to the use of model microbiomes in gnotobiotic mouse models has transformed our understanding of intestinal microbial ecology and the impact of the microbiome on the host. However, despite incredible advances, our understanding of the host-microbiome dialogue that shapes host physiology is still in its infancy. Progress has been limited by challenges associated with developing model systems that are both tractable enough to provide key mechanistic insights while also reflecting the enormous complexity of the gut ecosystem. Simplified model microbiomes have facilitated detailed interrogation of transcriptional and metabolic functions of the microbiome but do not recapitulate the interactions seen in complex communities. Conversely, intact complex communities from mice or humans provide a more physiologically relevant community type, but can limit our ability to uncover high-resolution insights into microbiome function. Moreover, complex microbiomes from lab-derived mice or humans often do not readily imprint human-like phenotypes. Therefore, improved model microbiomes that are highly defined and tractable, but that more accurately recapitulate human microbiome-induced phenotypic variation are required to improve understanding of fundamental processes governing host-microbiome mutualism. This improved understanding will enhance the translational relevance of studies that address how the microbiome promotes host health and influences disease states. Microbial exposures in wild mice, both symbiotic and infectious in nature, have recently been established to more readily recapitulate human-like phenotypes. The development of synthetic model communities from such “wild mice” therefore represents an attractive strategy to overcome the limitations of current approaches. Advances in microbial culturing approaches that allow for the generation of large and diverse libraries of isolates, coupled to ever more affordable large-scale genomic sequencing, mean that we are now ideally positioned to develop such systems. Furthermore, the development of sophisticated in vitro systems is allowing for detailed insights into host-microbiome interactions to be obtained. Here we discuss the need to leverage such approaches and highlight key challenges that remain to be addressed.

A Case of Neurosarcoidosis Mimicking Brain Tumor

2020 ◽  
Vol 16 ◽  
Author(s):  
Lutfullah Sari ◽  
Abdusselim Adil Peker ◽  
Dilek Hacer Cesme ◽  
Alpay Alkan
Keyword(s):  
Brain Tumor ◽  
Contrast Enhancement ◽  
Clinical Laboratory ◽  
Vasogenic Edema ◽  
Pulmonary Sarcoidosis ◽  
Brain Parenchyma ◽  
The Body ◽  
Oligoclonal Bands ◽  
Flair Sequence ◽  
History Of

Background: Neurosarcoidosis manifests symptomatically in 5% of patients with sarcoidosis and diagnosis can be challenging if not clinically suspected. Cerebral mass-like presentation of neurosarcoidosis rarely reported in the literature. We presented a woman with neurosarcoidosis who had a cerebral mass-like lesion which completely disappeared after medical treatment. Discussion: A 37-year-old woman with history of pulmonary sarcoidosis referred to the emergency service of our hospital with a one-month history of progressive dizziness, nausea and seeing flashing lights. At neurologic examination, numbness and weakness on the left side of the body, deviation of uvula toward the right side was seen. Cranial MRI demonstrated a 2.5x2 cm in size mass lesion which hypointense on T1 WI, heterogeneous hyperintense on T2 and FLAIR sequence with peripheral vasogenic edema and heterogeneous, irregular contrast enhancement simulating brain tumor. Also, leptomeningeal and nodular contrast enhancement was seen on brainstem, cerebellar vermis, perimesencephalic cistern and left frontal, bilateral parietooccipital sulcus. In laboratory tests; The level of serum angiotensin-converting enzyme (ACE) was 53 IU/mL (N:8-52 IU/mL) and cerebrospinal fluid (CSF) ACE was 23 IU/mL (N:0-2.6 IU/mL). CSF cytology analysis was normal. Pattern 2 oligoclonal bands were present. With these clinical, laboratory and radiological findings, cerebral involvement of sarcoidosis was suspected. Biopsy was not performed due to the high risk of morbidity caused by the deep location of the lesion.Patient was treated with methylprednisolone and Azathioprine for a month.On post-treatment control imaging; lesion disappeared completely without residual leptomeningeal and nodular contrast enhancement.Also, neurologic symptoms were decreased remarkably. Conclusion: Multi-system inflammatory disorders like sarcoidosis, can present with mass-like lesion in the brain parenchyma. While early diagnosis is important to prevent unnecessary interventions like biopsy and surgery, it is crucial to initiate the necessary treatment with the aim of recovery without sequelae. Radiological and clinical follow-up are fundamental in differential diagnosis.

scholarly journals Endocannabinoid system mediates the association between gut-microbial diversity and anhedonia/amotivation in a general population cohort

2021 ◽  
Author(s):  
Amedeo Minichino ◽  
Matthew A. Jackson ◽  
Marta Francesconi ◽  
Claire J. Steves ◽  
Cristina Menni ◽  
...  
Keyword(s):  
General Population ◽  
Microbial Diversity ◽  
Gut Microbiome ◽  
Endocannabinoid System ◽  
Alpha Diversity ◽  
Serum Levels ◽  
Population Cohort ◽  
Random Intercept ◽  
General Population Cohort ◽  
Antidepressant Use

AbstractAnhedonia and amotivation are debilitating symptoms and represent unmet therapeutic needs in a range of clinical conditions. The gut-microbiome-endocannabinoid axis might represent a potential modifiable target for interventions. Based on results obtained from animal models, we tested the hypothesis that the endocannabinoid system mediates the association between gut-microbiome diversity and anhedonia/amotivation in a general population cohort. We used longitudinal data collected from 786 volunteer twins recruited as part the TwinsUK register. Our hypothesis was tested with a multilevel mediation model using family structure as random intercept. The model was set using alpha diversity (within-individual gut-microbial diversity) as predictor, serum and faecal levels of the endocannabinoid palmitoylethanolamide (PEA) as mediator, and anhedonia/amotivation as outcome. PEA is considered the endogenous equivalent of cannabidiol, with increased serum levels believed to have anti-depressive effects, while increased stool PEA levels, reflecting increased excretion, are believed to have opposite, detrimental, effects on mental health. We therefore expected that either reduced serum PEA or increased stool PEA would mediate the association between microbial diversity and anhedonia amotivation. Analyses were adjusted for obesity, diet, antidepressant use, sociodemographic and technical covariates. Data were imputed using multiple imputation by chained equations. Mean age was 65.2 ± 7.6; 93% of the sample were females. We found a direct, significant, association between alpha diversity and anhedonia/amotivation (β = −0.37; 95%CI: −0.71 to −0.03; P = 0.03). Faecal, but not serum, levels of the endocannabinoid palmitoylethanolamide (PEA) mediated this association: the indirect effect was significant (β = −0.13; 95%CI: −0.24 to −0.01; P = 0.03), as was the total effect (β = −0.38; 95%CI: −0.72 to −0.04; P = 0.03), whereas the direct effect of alpha diversity on anhedonia/amotivation was attenuated fully (β = −0.25; 95%CI: −0.60 to 0.09; P = 0.16). Our results suggest that gut-microbial diversity might contribute to anhedonia/amotivation via the endocannabinoid system. These findings shed light on the biological underpinnings of anhedonia/amotivation and suggest the gut microbiota-endocannabinoid axis as a promising therapeutic target in an area of unmet clinical need.

scholarly journals Long-term Diet Quality and Gut Microbiome Functionality: A Prospective, Shotgun Metagenomic Study among Urban Chinese Adults

2021 ◽  
Vol 5 (4) ◽  
Author(s):  
Danxia Yu ◽  
Yaohua Yang ◽  
Jirong Long ◽  
Wanghong Xu ◽  
Qiuyin Cai ◽  
...  
Keyword(s):  
Diet Quality ◽  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Gene Families ◽  
Diet Group ◽  
Healthy Diet ◽  
Chinese Adults ◽  
Α Diversity ◽  
Unhealthy Diet

ABSTRACT Background Diet is known to affect human gut microbiome composition; yet, how diet affects gut microbiome functionality remains unclear. Objective We compared the diversity and abundance/presence of fecal microbiome metabolic pathways among individuals according to their long-term diet quality. Methods In 2 longitudinal cohorts, we assessed participants’ usual diets via repeated surveys during 1996–2011 and collected a stool sample in 2015–2018. Participants who maintained a healthy or unhealthy diet (i.e., stayed in the highest or lowest quintile of a healthy diet score throughout follow-up) were selected. Participants were excluded if they reported a history of cancer, cardiovascular disease, diabetes, or hypertension; had diarrhea or constipation in the last 7 d; or used antibiotics in the last 6 mo before stool collection. Functional profiling of shotgun metagenomics was performed using HUMAnN2. Associations of dietary variables and 420 microbial metabolic pathways were evaluated via multivariable-adjusted linear or logistic regression models. Results We included 144 adults (mean age = 64 y; 55% female); 66 had an unhealthy diet and 78 maintained a healthy diet. The healthy diet group had higher Shannon α-diversity indexes of microbial gene families and metabolic pathways (both P < 0.02), whereas β-diversity, as evaluated by Bray-Curtis distance, did not differ between groups (both P > 0.50). At P < 0.01 [false discovery rate (FDR) <0.15], the healthy diet group showed enriched pathways for vitamin and carrier biosynthesis (e.g., tetrahydrofolate, acetyl-CoA, and l-methionine) and tricarboxylic acid (TCA) cycle, and increased degradation (or reduced biosynthesis) of certain sugars [e.g., cytidine monophosphate (CMP)-legionaminate, deoxythymidine diphosphate (dTDP)-l-rhamnose, and sucrose], nucleotides, 4-aminobutanoate, methylglyoxal, sulfate, and aromatic compounds (e.g., catechol and toluene). Meanwhile, several food groups were associated with the CMP-legionaminate biosynthesis pathway at FDR <0.05. Conclusions In a small longitudinal study of generally healthy, older Chinese adults, we found long-term healthy eating was associated with increased α-diversity of microbial gene families and metabolic pathways and altered symbiotic functions relevant to human nutrition and health.

scholarly journals Adopting seasonal regimen (Ritucharya) to modulate the seasonal variation in gut microbiome

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Deepthi. R ◽  
Vandana Rani M ◽  
Delvin T. Robin ◽  
Anusree Dileep
Keyword(s):  
Public Health ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Health Management ◽  
Disease Process ◽  
The Body ◽  
Leaky Gut ◽  
Human Gut ◽  
Extrinsic Factors ◽  
Application Prospects

AbstractThe science of Ayurveda with its strong and unique fundamentals holds its domain forever amidst all scientific and medical advancements. The concept of Shadkriyakala (the different phases of disease formation) holds relevance in preventive medicine and public health management as it provides ample chance to halt the disease process at each stage by timely intervention. In this review, we would like to bring to the limelight the relevance of Ritucharya (seasonal regimen) in primary prevention by modulating the gut microbiota. The modern gut microbiome researches now help us to better explore the Ayurveda theories of Agni (digestive fire) and Ama (metabolic toxins) preached centuries back. Ayurveda firmly proclaims that no disease ever arises without the derangement of Agni (digestive fire). The whole preventive and treatment methodology in Ayurveda focuses upon the modulation and management of “Agni” (digestive fire). When the functioning of Agni is deranged, Ama (metabolic toxin) is produced and it vitiates the doshas which spread throughout the body and manifest as varied diseases. A biomedical perspective of our reviews suggests that dysbiosis of microbial flora can cause a leaky gut by which the toxins of deranged digestive metabolism enter the bloodstream. Consequently, an inflammatory response occurs within the body which expresses out as diseases opportunistically. We meticulously reviewed the influence of extrinsic factors namely diet and climate on human gut microbiota, and our analysis emphasises the application prospects of Ritucharya (seasonal regimen), in regulating the dynamic host-microbe interaction.

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